Current steering to activate targeted neural pathways during deep brain stimulation of the subthalamic region

Deep brain stimulation (DBS) has steadily evolved into an established surgical therapy for numerous neurological disorders, most notably Parkinson's disease (PD). Traditional DBS technology relies on voltage-controlled stimulation with a single source; however, recent engineering advances are providing current-controlled devices with multiple independent sources. These new stimulators deliver constant current to the brain tissue, irrespective of impedance changes that occur around the electrode, and enable more specific steering of current towards targeted regions of interest. In this study, we examined the impact of current steering between multiple electrode contacts to directly activate three distinct neural populations in the subthalamic region commonly stimulated for the treatment of PD: projection neurons of the subthalamic nucleus (STN), globus pallidus internus (GPi) fibers of the lenticular fasiculus, and internal capsule (IC) fibers of passage. We used three-dimensional finite element electric field models, along with detailed multicompartment cable models of the three neural populations to determine their activations using a wide range of stimulation parameter settings. Our results indicate that selective activation of neural populations largely depends on the location of the active electrode(s). Greater activation of the GPi and STN populations (without activating any side effect related IC fibers) was achieved by current steering with multiple independent sources, compared to a single current source. Despite this potential advantage, it remains to be seen if these theoretical predictions result in a measurable clinical effect that outweighs the added complexity of the expanded stimulation parameter search space generated by the more flexible technology.

[1]  Uwe Walter,et al.  No Lewy pathology in monkeys with over 10 years of severe MPTP Parkinsonism , 2009, Movement disorders : official journal of the Movement Disorder Society.

[2]  Harald Treuer,et al.  Intraoperative X-Ray Detection and MRI-Based Quantification of Brain Shift Effects Subsequent to Implantation of the First Electrode in Bilateral Implantation of Deep Brain Stimulation Electrodes , 2009, Stereotactic and Functional Neurosurgery.

[3]  P. Krack,et al.  Deep-brain stimulation of the subthalamic nucleus or the pars interna of the globus pallidus in Parkinson's disease. , 2001, The New England journal of medicine.

[4]  Matthew D. Johnson,et al.  In vivo impedance spectroscopy of deep brain stimulation electrodes , 2009, Journal of neural engineering.

[5]  Svjetlana Miocinovic,et al.  Computational analysis of deep brain stimulation , 2007, Expert review of medical devices.

[6]  Nicholas T. Carnevale,et al.  The NEURON Simulation Environment , 1997, Neural Computation.

[7]  Murtaza Z Mogri,et al.  Optical Deconstruction of Parkinsonian Neural Circuitry , 2009, Science.

[8]  C. McIntyre,et al.  Excitation of central nervous system neurons by nonuniform electric fields. , 1999, Biophysical journal.

[9]  C. McIntyre,et al.  Electric field and stimulating influence generated by deep brain stimulation of the subthalamic nucleus , 2004, Clinical Neurophysiology.

[10]  Gordon L. Kindlmann,et al.  Tensorlines: advection-diffusion based propagation through diffusion tensor fields , 1999, Proceedings Visualization '99 (Cat. No.99CB37067).

[11]  C. McIntyre,et al.  Reversing cognitive-motor impairments in Parkinson's disease patients using a computational modelling approach to deep brain stimulation programming. , 2010, Brain : a journal of neurology.

[12]  Matthew D. Johnson,et al.  Current-controlled deep brain stimulation reduces in vivo voltage fluctuations observed during voltage-controlled stimulation , 2010, Clinical Neurophysiology.

[13]  Elena Moro,et al.  Subthalamic nucleus stimulation: improvements in outcome with reprogramming. , 2006, Archives of neurology.

[14]  C. McIntyre,et al.  Extracellular stimulation of central neurons: influence of stimulus waveform and frequency on neuronal output. , 2002, Journal of neurophysiology.

[15]  S. Wakana,et al.  Fiber tract-based atlas of human white matter anatomy. , 2004, Radiology.

[16]  Svjetlana Miocinovic,et al.  Computational analysis of subthalamic nucleus and lenticular fasciculus activation during therapeutic deep brain stimulation. , 2006, Journal of neurophysiology.

[17]  Benoit M. Dawant,et al.  Effect of brain shift on the creation of functional atlases for deep brain stimulation surgery , 2010, International Journal of Computer Assisted Radiology and Surgery.

[18]  Y. Ben-Shlomo,et al.  Stimulation of the caudal zona incerta is superior to stimulation of the subthalamic nucleus in improving contralateral parkinsonism. , 2006, Brain : a journal of neurology.

[19]  C. Blaha,et al.  Dopamine efflux in the rat striatum evoked by electrical stimulation of the subthalamic nucleus: potential mechanism of action in Parkinson's disease , 2006, The European journal of neuroscience.

[20]  A. Dale,et al.  Conductivity tensor mapping of the human brain using diffusion tensor MRI , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[21]  Svjetlana Miocinovic,et al.  Dissociation of motor symptoms during deep brain stimulation of the subthalamic nucleus in the region of the internal capsule , 2011, Experimental Neurology.

[22]  A. Parent,et al.  Axonal branching pattern of neurons of the subthalamic nucleus in primates , 2000, The Journal of comparative neurology.

[23]  A. Parent,et al.  The pallidofugal motor fiber system in primates. , 2004, Parkinsonism & related disorders.

[24]  Cameron C McIntyre,et al.  Evaluation of novel stimulus waveforms for deep brain stimulation , 2010, Journal of neural engineering.

[25]  J Meixensberger,et al.  The first evaluation of brain shift during functional neurosurgery by deformation field analysis , 2005, Journal of Neurology, Neurosurgery & Psychiatry.

[26]  J. Bullier,et al.  Axons, but not cell bodies, are activated by electrical stimulation in cortical gray matter II. Evidence from selective inactivation of cell bodies and axon initial segments , 1998, Experimental Brain Research.

[27]  Daniel R. Merrill,et al.  Electrical stimulation of excitable tissue: design of efficacious and safe protocols , 2005, Journal of Neuroscience Methods.

[28]  Jaimie M. Henderson,et al.  Patient-specific analysis of the volume of tissue activated during deep brain stimulation , 2007, NeuroImage.

[29]  Grant D. Huang,et al.  Bilateral deep brain stimulation vs best medical therapy for patients with advanced Parkinson disease: a randomized controlled trial. , 2009, JAMA.

[30]  C. McIntyre,et al.  Patient-specific models of deep brain stimulation: Influence of field model complexity on neural activation predictions , 2010, Brain Stimulation.

[31]  C. McIntyre,et al.  Current steering to control the volume of tissue activated during deep brain stimulation , 2008, Brain Stimulation.

[32]  J. Bullier,et al.  Axons, but not cell bodies, are activated by electrical stimulation in cortical gray matter I. Evidence from chronaxie measurements , 1998, Experimental Brain Research.

[33]  Robert E. Gross,et al.  Assessment of Brain Shift Related to Deep Brain Stimulation Surgery , 2007, Stereotactic and Functional Neurosurgery.

[34]  C. McIntyre,et al.  Modeling the excitability of mammalian nerve fibers: influence of afterpotentials on the recovery cycle. , 2002, Journal of neurophysiology.